A conditional allele of Rspo3 reveals redundant function of R-spondins during mouse limb development

R‐spondins are secreted ligands that bind cell surface receptors and activate Wnt/β‐catenin signaling. Human mutations and gene inactivation studies in mice have revealed a role for these four proteins (RSPO1‐4) in diverse developmental processes ranging from sex determination to limb development. A...

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Bibliographic Details
Published in:	Genesis (New York, N.Y. : 2000) Vol. 50; no. 10; pp. 741 - 749
Main Authors:	Neufeld, Stanley, Rosin, Jessica M., Ambasta, Anshula, Hui, Kristen, Shaneman, Venessa, Crowder, Ray, Vickerman, Lori, Cobb, John
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-10-2012
Subjects:	Alleles Animals conditional inactivation Cre Extremities - embryology Gene Expression Regulation, Developmental Limb Deformities, Congenital - genetics Mice Mice, Transgenic Thrombospondins - genetics Thrombospondins - metabolism Transcription, Genetic Wnt signaling β-catenin
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Summary:	R‐spondins are secreted ligands that bind cell surface receptors and activate Wnt/β‐catenin signaling. Human mutations and gene inactivation studies in mice have revealed a role for these four proteins (RSPO1‐4) in diverse developmental processes ranging from sex determination to limb development. Among the genes coding for R‐spondins, only inactivation of Rspo3 shows early embryonic lethality (E10.5 in mice). Therefore, a conditional allele of this gene is necessary to understand the function of R‐spondins throughout murine development. To address this need, we have produced an allele in which loxP sites flank exons 2–4 of Rspo3, allowing tissue‐specific deletion of these exons in the presence of Cre recombinase. We used these mice to investigate the role of Rspo3 during limb development and found that limbs ultimately developed normally in the absence of Rspo3 function. However, severe hindlimb truncations resulted when Rspo3 and Rspo2 mutations were combined, demonstrating redundant function of these genes. genesis 50:741–749, 2012. © 2012 Wiley Periodicals, Inc.
Bibliography:	Natural Sciences and Engineering Research Council of Canada (NSERC) ArticleID:DVG22040 ark:/67375/WNG-PV1MSX0P-4 Canadian Institutes of Health Research (CIHR) - No. MOP-93562 istex:7B7200CEAB5385F2750511B4C277F92169D7D78F ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1526-954X 1526-968X
DOI:	10.1002/dvg.22040